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犬麻疹病毒感染诱导未折叠蛋白反应的三个分支、丝裂原活化蛋白激酶(MAPK)和细胞凋亡的激活。

Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis.

作者信息

Colina Santiago Emanuel, Williman Macarena Marta, Tizzano Marco Antonio, Serena María Soledad, Echeverría María Gabriela, Metz Germán Ernesto

机构信息

Laboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Cientìficas y Técnicas (CONICET), CCT-La Plata, La Plata CP 1900, Buenos Aires, Argentina.

出版信息

Viruses. 2024 Nov 28;16(12):1846. doi: 10.3390/v16121846.

DOI:10.3390/v16121846
PMID:39772156
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11680218/
Abstract

, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the family. In dogs (), common signs of infection include conjunctivitis, digital hyperkeratosis and neuropathologies. Even with vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes have been an interesting and promising area in new therapeutic drugs research in recent years. It is known that in the process of virus infection, the endoplasmic reticulum (ER) loses its homeostasis, inducing stress and the subsequent unfolded protein response or UPR in which three ER-trans-membrane proteins are implicated: PERK, IRE1 and ATF6. Moreover, in prolonged ER stress, the apoptosis is induced through the CHOP, as a final step of viral infection. Cell culture and molecular techniques such as RT-qPCR and RT-PCR were used in the present study. We demonstrate the activation in vitro of the three UPR pathways after infection with an attenuated strain of CDV. Also, the implication of a MAPK pathway through the p38 protein and the apoptotic CHOP was demonstrated to contribute to the process of infection. Even more, our study suggested that CDV replication occurs in a PERK-dependent manner.

摘要

通常被称为犬瘟热病毒(CDV),是一种麻疹病毒,与该科的多种症状有关。在犬类中,常见的感染症状包括结膜炎、趾部角化过度和神经病理学症状。即使进行了疫苗接种,犬瘟热疾病在全球范围内仍然存在,因此近年来,感染过程中涉及的分子途径一直是新型治疗药物研究中一个有趣且有前景的领域。众所周知,在病毒感染过程中,内质网(ER)失去其稳态,引发应激以及随后的未折叠蛋白反应或UPR,其中涉及三种内质网跨膜蛋白:PERK、IRE1和ATF6。此外,在长期内质网应激中,通过CHOP诱导细胞凋亡,这是病毒感染的最后一步。本研究使用了细胞培养和分子技术,如RT-qPCR和RT-PCR。我们证明了用减毒的CDV株感染后,三种UPR途径在体外被激活。此外,还证明了通过p38蛋白的丝裂原活化蛋白激酶(MAPK)途径和凋亡相关的CHOP参与了感染过程。甚至,我们的研究表明CDV复制以PERK依赖的方式发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/b4a6f2304379/viruses-16-01846-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/5b3d33535617/viruses-16-01846-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/b2e7778d1727/viruses-16-01846-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/57b5c4b906d5/viruses-16-01846-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/b4a6f2304379/viruses-16-01846-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/5b3d33535617/viruses-16-01846-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/b2e7778d1727/viruses-16-01846-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/57b5c4b906d5/viruses-16-01846-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bcc/11680218/b4a6f2304379/viruses-16-01846-g008.jpg

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本文引用的文献

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Viruses. 2024 Sep 30;16(10):1555. doi: 10.3390/v16101555.
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Direct interaction of the molecular chaperone GRP78/BiP with the Newcastle disease virus hemagglutinin-neuraminidase protein plays a vital role in viral attachment to and infection of culture cells.分子伴侣 GRP78/BiP 与新城疫病毒血凝素-神经氨酸酶蛋白的直接相互作用在病毒附着和感染培养细胞中起着至关重要的作用。
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The H protein of attenuated canine distemper virus is degraded via endoplasmic reticulum-associated protein degradation.
减毒犬瘟热病毒的H蛋白通过内质网相关蛋白降解途径被降解。
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Peste des Petits Ruminants Virus Upregulates STING to Activate ATF6-Mediated Autophagy.小反刍兽疫病毒上调 STING 以激活 ATF6 介导的自噬。
J Virol. 2022 Oct 26;96(20):e0137522. doi: 10.1128/jvi.01375-22. Epub 2022 Oct 5.
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GRP78, a Novel Host Factor for SARS-CoV-2: The Emerging Roles in COVID-19 Related to Metabolic Risk Factors.GRP78,一种新型的新冠病毒宿主因子:其在与代谢风险因素相关的新冠肺炎中的新作用
Biomedicines. 2022 Aug 17;10(8):1995. doi: 10.3390/biomedicines10081995.
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Endoplasmic Reticulum Chaperones in Viral Infection: Therapeutic Perspectives.内质网伴侣蛋白在病毒感染中的作用:治疗新视角。
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